Blood glucose levels, often referred to as blood sugar levels or concentrations, refer to the amount of glucose present in the blood of a human or animal. Blood glucose levels fluctuate throughout the day, being lowest in the morning before eating, rising for an hour or two following each meal. The primary function of glucose is a source of energy. Glucose from the diet enters the bloodstream from the intestines and is made available for cell absorption via insulin. Glucose may also be produced endogenously from carbohydrates or amino acid R-group side chain substrates through gluconeogenesis when sufficient dietary glucose is available.
The levels of glucose in the blood are tightly regulated in mammals by metabolic processes. The human body maintains glucose levels at close to constant levels most of the day. Insulin signaling directs the body's cells to take up glucose for their own use. If the glucose level inside cells is high, some glucose will be converted to the insoluble glycogen to prevent the soluble glucose from interfering with cellular metabolism. This lowers blood glucose levels and helps prevent hyperglycemia. A deficiency in insulin or the compromised ability to respond to insulin leads to diabetes. Glycogen is held as an energy reserve in the liver and in muscle tissue. If a person's glycogen stores are full, extra glucose will be converted to fat and stored.
Hyperglycemia refers to a state of persistently high levels of blood glucose. Diabetes mellitus is the most prominent disease resulting from a failure of blood sugar regulation. The classical symptoms of high blood sugar include frequent urination (polyuria), increased thirst (polydipsia) and increased hunger (polyphagia). Long term complications directly linked to hyperglycemia include cardiovascular disease, chronic renal failure, and diabetic retinopathy.
Type I diabetes results from the body's failure to produce insulin, and is sometimes referred to as insulin-dependent diabetes or juvenile diabetes. Those suffering from type I diabetes typically control insulin levels, and consequently blood glucose levels, by injecting insulin. Type II diabetes stems from resistance to insulin, where cells fail to use or respond to insulin properly, and is sometimes referred to as adult-onset diabetes. Both type I and type II diabetes are chronic conditions that cannot be cured. Medical intervention therefore targets prevention of hyperglycemia and also management of the symptoms once hyperglycemia has been diagnosed.
Milk, mainly bovine milk, consumed in populations throughout the world, is a major source of protein in human diets. Bovine milk typically comprises around 30 grams per litre of protein. Caseins make up the largest component (80%) of that protein, and beta-caseins make up about 37% of the caseins. In the past two decades the body of evidence implicating casein proteins, especially beta-caseins, in a number of health disorders has been growing.
The beta-caseins can be categorised as beta-casein A1 and beta-casein A2. These two proteins are the predominant beta-caseins in milk consumed in most human populations. Beta-casein A1 differs from beta-casein A2 by a single amino acid. A histidine amino acid is located at position 67 of the 209 amino acid sequence of beta-casein A1, whereas a proline is located at the same position of beta-casein A2. This single amino acid difference is, however, critically important to the enzymatic digestion of beta-caseins in the gut. The presence of histidine at position 67 allows a protein fragment comprising seven amino acids, known as beta-casomorphin-7 (BCM-7), to be produced on enzymatic digestion. Thus, BCM-7 is a digestion product of beta-casein A1. In the case of beta-casein A2, position 67 is occupied by a proline which hinders cleavage of the amino acid bond at that location. Thus, BCM-7 is not a digestion product of beta-casein A2.
Other beta-casein variants, such as beta-casein B and beta-casein C, also have histidine at position 67, and other variants, such as A3, D and E, have proline at position 67. But these variants are found only in very low levels, or not found at all, in milk from cows of European origin. Thus, in the context of this invention, the term beta-casein A1 refers to any beta-casein having histidine at position 67, and the term beta-casein A2 refers to any beta-casein having proline at position 67.
BCM-7 is an opioid peptide and can potently activate opioid receptors throughout the body. BCM-7 has the ability to cross the gastrointestinal wall and enter circulation enabling it to influence systemic and cellular activities via opioid receptors. The applicant and others have previously determined a link between the consumption of beta-casein A1 in milk and milk products and the incidence of certain health conditions including type I diabetes (WO 1996/014577), coronary heart disease (WO 1996/036239) and neurological disorders (WO 2002/019832). WO 1996/014577 describes the triggering of type I diabetes in humans by the ingestion of milk and milk products that contain beta-casein A1. It is considered that beta-casein A1 stimulates diabetogenic activity, i.e. may cause humans to become diabetic.
The applicant has now found conclusive scientific evidence for a direct link between the consumption of beta-casein A1 and blood glucose levels, and also the consumption of beta-casein A1 and the development of insulin resistance. Since elevated blood glucose levels are implicated in a number of adverse health conditions, including types I and II diabetes, and weight management conditions such as metabolic syndrome (syndrome X) and obesity, the applicant has found a new way to treat these conditions or manage the symptoms of these conditions. Importantly, the applicant has found evidence, not only of an acute and undesirable response to the consumption of beta-casein A1, but also of an ongoing (post-exposure to beta-casein A1 or BCM-7) response in that the consumption of beta-casein A1, and resultant production of BCM-7, can induce genetic changes in an animal that lead to higher levels of blood glucose and consequently an increased likelihood of causing symptoms associated with high blood glucose levels.
It is therefore an object of the invention to provide a method for controlling the levels of glucose in blood, or to at least provide a useful alternative to existing methods.